@article{LudwigSaemannAlexanderetal.2013, author = {Ludwig, K. U. and S{\"a}mann, P. and Alexander, M. and Becker, J. and Bruder, J. and Moll, K. and Spieler, D. and Czisch, M. and Warnke, A. and Docherty, S. J. and Davis, O. S. P. and Plomin, R. and N{\"o}then, M. M. and Landerl, K. and M{\"u}ller-Myhsok, B. and Hoffmann, P. and Schumacher, J. and Schulte-K{\"o}rne, G. and Czamara, D.}, title = {A common variant in Myosin-18B contributes to mathematical abilities in children with dyslexia and intraparietal sulcus variability in adults}, series = {Translational Psychiatry}, volume = {3}, journal = {Translational Psychiatry}, number = {e229}, doi = {10.1038/tp.2012.148}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-131513}, year = {2013}, abstract = {The ability to perform mathematical tasks is required in everyday life. Although heritability estimates suggest a genetic contribution, no previous study has conclusively identified a genetic risk variant for mathematical performance. Research has shown that the prevalence of mathematical disabilities is increased in children with dyslexia. We therefore correlated genome-wide data of 200 German children with spelling disability, with available quantitative data on mathematic ability. Replication of the top findings in additional dyslexia samples revealed that rs133885 was a genome-wide significant marker for mathematical abilities\((P_{comb}=7.71 x 10^{-10}, n=699)\), with an effect size of 4.87\%. This association was also found in a sample from the general population (P=0.048, n=1080), albeit with a lower effect size. The identified variant encodes an amino-acid substitution in MYO18B, a protein with as yet unknown functions in the brain. As areas of the parietal cortex, in particular the intraparietal sulcus (IPS), are involved in numerical processing in humans, we investigated whether rs133885 was associated with IPS morphology using structural magnetic resonance imaging data from 79 neuropsychiatrically healthy adults. Carriers of the MYO18B risk-genotype displayed a significantly lower depth of the right IPS. This validates the identified association between rs133885 and mathematical disability at the level of a specific intermediate phenotype.}, language = {en} } @article{MuellerBuchholtzLeyhausenPetersonetal.1987, author = {M{\"u}ller-Buchholtz, W. and Leyhausen, G. and Peterson, P. and Schubert, G. and Ulrichs, Karin}, title = {A simple methodological principle for large scale extraction and purification of collagenase-digested islets}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-44770}, year = {1987}, abstract = {No abstract available}, subject = {Chirurgie}, language = {en} } @article{MuellerBroeckerKlinkeretal.2012, author = {M{\"u}ller, P.A. and Br{\"o}cker, E.B. and Klinker, E. and Stoevesandt, J. and Benoit, S.}, title = {Adjuvant treatment of recalcitrant Bullous pemphigoid with immunoadsorption}, series = {Dermatology}, volume = {224}, journal = {Dermatology}, number = {3}, issn = {1018-8665}, doi = {10.1159/000339071}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-196620}, pages = {224 -- 227}, year = {2012}, abstract = {Elimination of pathogenic autoantibodies by immunoadsorption (IA) has been described as an effective adjuvant treatment in severe bullous autoimmune diseases, especially in pemphigus. There is much less experience in the treatment of bullous pemphigoid (BP). BP was diagnosed in a 62-year-old Caucasian woman presenting a pruritic rash with multiple tense blisters. Standard treatments with topical and oral corticosteroids, steroid-sparing agents including dapsone, azathioprine, mycophenolate mofetil (MMF) and intravenous immunoglobulins were ineffective or had to be discontinued due to adverse events. An immediate clinical response could be achieved by two treatment cycles of adjuvant protein A immunoadsorption (PA-IA) in addition to continued treatment with MMF (2 g/day) and prednisolone (1 mg/kg/day). Tolerance was excellent. Clinical improvement remained stable after discontinuation of IA and went along with sustained reduction of circulating autoantibodies. Our data demonstrate that PA-IA might be a safe and effective adjuvant treatment in severe and recalcitrant BP.}, language = {en} } @article{HerrmannMuellerGraffKaulitzetal.2022, author = {Herrmann, David P. and M{\"u}ller-Graff, Franz-Tassilo and Kaulitz, Stefan and Cebulla, Mario and Kurz, Anja and Hagen, Rudolf and Neun, Tilmann and Rak, Kristen}, title = {Application of intentional facial nerve stimulation during cochlear implantation as an electrophysiological tool to estimate the intracochlear electrode position}, series = {Scientific Reports}, volume = {12}, journal = {Scientific Reports}, number = {1}, doi = {10.1038/s41598-022-17732-9}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-300197}, year = {2022}, abstract = {This proof of concept describes the use of evoked electromyographic (EMG) activation of the facial nerve for intraoperative monitoring of the electrode insertion during cochlear implantation (CI). Intraoperative EMG measurements from the facial nerve were conducted in nine patients undergoing CI implantation. Electric current pulses were emitted from contacts on the CI array during and immediately after electrode insertion. For control, the results of EMG measurements were compared to postoperative flat panel volume computed tomography scans with secondary reconstruction (fpVCT\(_{SECO}\)). During insertion, the EMG response evoked by the electrical stimulation from the CI was growing with the stimulating contact approaching the facial nerve and declined with increasing distance. After full insertion, contacts on the apical half of the CI array stimulated higher EMG responses compared with those on the basal half. Comparison with postoperative imaging demonstrated that electrode contacts stimulating high EMG responses had the shortest distances to the facial nerve. It could be demonstrated that electrically evoked EMG activation of the facial nerve can be used to monitor the progress during CI electrode insertion and to control the intracochlear electrode position after full insertion.}, language = {en} } @article{ZeinerZinkeKowalewskietal.2018, author = {Zeiner, P. S. and Zinke, J. and Kowalewski, D. J. and Bernatz, S. and Tichy, J. and Ronellenfitsch, M. W. and Thorsen, F. and Berger, A. and Forster, M. T. and Muller, A. and Steinbach, J. P. and Beschorner, R. and Wischhusen, J. and Kvasnicka, H. M. and Plate, K. H. and Stefanović, S. and Weide, B. and Mittelbronn, M. and Harter, P. N.}, title = {CD74 regulates complexity of tumor cell HLA class II peptidome in brain metastasis and is a positive prognostic marker for patient survival}, series = {Acta Neuropathologica Communications}, volume = {6}, journal = {Acta Neuropathologica Communications}, doi = {10.1186/s40478-018-0521-5}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-233882}, year = {2018}, abstract = {Abstract Despite multidisciplinary local and systemic therapeutic approaches, the prognosis for most patients with brain metastases is still dismal. The role of adaptive and innate anti-tumor response including the Human Leukocyte Antigen (HLA) machinery of antigen presentation is still unclear. We present data on the HLA class II-chaperone molecule CD74 in brain metastases and its impact on the HLA peptidome complexity. We analyzed CD74 and HLA class II expression on tumor cells in a subset of 236 human brain metastases, primary tumors and peripheral metastases of different entities in association with clinical data including overall survival. Additionally, we assessed whole DNA methylome profiles including CD74 promoter methylation and differential methylation in 21 brain metastases. We analyzed the effects of a siRNA mediated CD74 knockdown on HLA-expression and HLA peptidome composition in a brain metastatic melanoma cell line. We observed that CD74 expression on tumor cells is a strong positive prognostic marker in brain metastasis patients and positively associated with tumor-infiltrating T-lymphocytes (TILs). Whole DNA methylome analysis suggested that CD74 tumor cell expression might be regulated epigenetically via CD74 promoter methylation. CD74\(^{high}\) and TIL\(^{high}\) tumors displayed a differential DNA methylation pattern with highest enrichment scores for antigen processing and presentation. Furthermore, CD74 knockdown in vitro lead to a reduction of HLA class II peptidome complexity, while HLA class I peptidome remained unaffected. In summary, our results demonstrate that a functional HLA class II processing machinery in brain metastatic tumor cells, reflected by a high expression of CD74 and a complex tumor cell HLA peptidome, seems to be crucial for better patient prognosis.}, language = {en} } @article{SchuemannGrossBaueretal.2021, author = {Sch{\"u}mann, Franziska Lea and Groß, Elisabeth and Bauer, Marcus and Rohde, Christian and Sandmann, Sarah and Terziev, Denis and M{\"u}ller, Lutz P. and Posern, Guido and Wienke, Andreas and Fend, Falko and Hansmann, Martin-Leo and Klapper, Wolfram and Rosenwald, Andreas and Stein, Harald and Dugas, Martin and M{\"u}ller-Tidow, Carsten and Wickenhauser, Claudia and Binder, Mascha and Weber, Thomas}, title = {Divergent effects of EZH1 and EZH2 protein expression on the prognosis of patients with T-cell lymphomas}, series = {Biomedicines}, volume = {9}, journal = {Biomedicines}, number = {12}, issn = {2227-9059}, doi = {10.3390/biomedicines9121842}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-252155}, year = {2021}, abstract = {T-cell lymphomas are highly heterogeneous and their prognosis is poor under the currently available therapies. Enhancers of zeste homologue 1 and 2 (EZH1/2) are histone H3 lysine-27 trimethyltransferases (H3K27me3). Despite the rapid development of new drugs inhibiting EZH2 and/or EZH1, the molecular interplay of these proteins and the impact on disease progression and prognosis of patients with T-cell lymphomas remains insufficiently understood. In this study, EZH1/2 mutation status was evaluated in 33 monomorphic epitheliotropic intestinal T-cell lymphomas by next generation sequencing and EZH1/2 and H3K27me3 protein expression levels were detected by immunohistochemistry in 46 T-cell lymphomas. Correlations with clinicopathologic features were analyzed and survival curves generated. No EZH1 mutations and one (3\%) EZH2 missense mutation were identified. In univariable analysis, high EZH1 expression was associated with an improved overall survival (OS) and progression-free survival (PFS) whereas high EZH2 and H3K27me3 expression were associated with poorer OS and PFS. Multivariable analysis revealed EZH1 (hazard ratio (HR) = 0.183; 95\% confidence interval (CI): 0.044-0.767; p = 0.020;) and EZH2 (HR = 8.245; 95\% CI: 1.898-35.826; p = 0.005) to be independent, divergent prognostic markers for OS. In conclusion, EZH1/2 protein expression had opposing effects on the prognosis of T-cell lymphoma patients.}, language = {en} } @article{ThornChaoGeorgievetal.2020, author = {Thorn, Simon and Chao, Anne and Georgiev, Konstadin B. and M{\"u}ller, J{\"o}rg and B{\"a}ssler, Claus and Campbell, John L. and Jorge, Castro and Chen, Yan-Han and Choi, Chang-Yong and Cobb, Tyler P. and Donato, Daniel C. and Durska, Ewa and Macdonald, Ellen and Feldhaar, Heike and Fontaine, Jospeh B. and Fornwalt, Paula J. and Hern{\´a}ndez Hern{\´a}ndez, Raquel Mar{\´i}a and Hutto, Richard L. and Koivula, Matti and Lee, Eun-Jae and Lindenmayer, David and Mikusinski, Grzegorz and Obrist, Martin K. and Perl{\´i}k, Michal and Rost, Josep and Waldron, Kaysandra and Wermelinger, Beat and Weiß, Ingmar and Zmihorski, Michal and Leverkus, Alexandro B.}, title = {Estimating retention benchmarks for salvage logging to protect biodiversity}, series = {Nature Communications}, volume = {11}, journal = {Nature Communications}, doi = {10.1038/s41467-020-18612-4}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-230512}, year = {2020}, abstract = {Forests are increasingly affected by natural disturbances. Subsequent salvage logging, a widespread management practice conducted predominantly to recover economic capital, produces further disturbance and impacts biodiversity worldwide. Hence, naturally disturbed forests are among the most threatened habitats in the world, with consequences for their associated biodiversity. However, there are no evidence-based benchmarks for the proportion of area of naturally disturbed forests to be excluded from salvage logging to conserve biodiversity. We apply a mixed rarefaction/extrapolation approach to a global multi-taxa dataset from disturbed forests, including birds, plants, insects and fungi, to close this gap. We find that 757\% (mean +/- SD) of a naturally disturbed area of a forest needs to be left unlogged to maintain 90\% richness of its unique species, whereas retaining 50\% of a naturally disturbed forest unlogged maintains 73 +/- 12\% of its unique species richness. These values do not change with the time elapsed since disturbance but vary considerably among taxonomic groups. Salvage logging has become a common practice to gain economic returns from naturally disturbed forests, but it could have considerable negative effects on biodiversity. Here the authors use a recently developed statistical method to estimate that ca. 75\% of the naturally disturbed forest should be left unlogged to maintain 90\% of the species unique to the area.}, language = {en} } @article{PeterBultinckMyantetal.2014, author = {Peter, Stefanie and Bultinck, Jennyfer and Myant, Kevin and Jaenicke, Laura A. and Walz, Susanne and M{\"u}ller, Judith and Gmachl, Michael and Treu, Matthias and Boehmelt, Guido and Ade, Casten P. and Schmitz, Werner and Wiegering, Armin and Otto, Christoph and Popov, Nikita and Sansom, Owen and Kraut, Norbert and Eilers, Martin}, title = {H Tumor cell-specific inhibition of MYC function using small molecule inhibitors of the HUWE1 ubiquitin ligase}, series = {EMBO Molecular Medicine}, volume = {6}, journal = {EMBO Molecular Medicine}, number = {12}, issn = {1757-4684}, doi = {10.15252/emmm.201403927}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-118132}, pages = {1525-41}, year = {2014}, abstract = {Deregulated expression of MYC is a driver of colorectal carcinogenesis, necessitating novel strategies to inhibit MYC function. The ubiquitin ligase HUWE1 (HECTH9, ARF-BP1, MULE) associates with both MYC and the MYC-associated protein MIZ1. We show here that HUWE1 is required for growth of colorectal cancer cells in culture and in orthotopic xenograft models. Using high-throughput screening, we identify small molecule inhibitors of HUWE1, which inhibit MYC-dependent transactivation in colorectal cancer cells, but not in stem and normal colon epithelial cells. Inhibition of HUWE1 stabilizes MIZ1. MIZ1 globally accumulates on MYC target genes and contributes to repression of MYC-activated target genes upon HUWE1 inhibition. Our data show that transcriptional activation by MYC in colon cancer cells requires the continuous degradation of MIZ1 and identify a novel principle that allows for inhibition of MYC function in tumor cells.}, language = {en} } @article{HoubenHesbacherSchmidetal.2011, author = {Houben, Roland and Hesbacher, Sonja and Schmid, Corinna P. and Kauczok, Claudia S. and Flohr, Ulrike and Haferkamp, Sebastian and M{\"u}ller, Cornelia S. L. and Schrama, David and Wischhusen, J{\"o}rg and Becker, J{\"u}rgen C.}, title = {High-Level Expression of Wild-Type p53 in Melanoma Cells is Frequently Associated with Inactivity in p53 Reporter Gene Assays}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-69012}, year = {2011}, abstract = {Background: Inactivation of the p53 pathway that controls cell cycle progression, apoptosis and senescence, has been proposed to occur in virtually all human tumors and p53 is the protein most frequently mutated in human cancer. However, the mutational status of p53 in melanoma is still controversial; to clarify this notion we analysed the largest series of melanoma samples reported to date. Methodology/Principal Findings: Immunohistochemical analysis of more than 180 melanoma specimens demonstrated that high levels of p53 are expressed in the vast majority of cases. Subsequent sequencing of the p53 exons 5-8, however, revealed only in one case the presence of a mutation. Nevertheless, by means of two different p53 reporter constructs we demonstrate transcriptional inactivity of wild type p53 in 6 out of 10 melanoma cell lines; the 4 other p53 wild type melanoma cell lines exhibit p53 reporter gene activity, which can be blocked by shRNA knock down of p53. Conclusions/Significance: In melanomas expressing high levels of wild type p53 this tumor suppressor is frequently inactivated at transcriptional level.}, subject = {Krebs }, language = {en} } @article{HerrmannMuellerOrthetal.2020, author = {Herrmann, Andreas B. and M{\"u}ller, Martha-Lena and Orth, Martin F. and M{\"u}ller, J{\"o}rg P. and Zernecke, Alma and Hochhaus, Andreas and Ernst, Thomas and Butt, Elke and Frietsch, Jochen J.}, title = {Knockout of LASP1 in CXCR4 expressing CML cells promotes cell persistence, proliferation and TKI resistance}, series = {Journal of Cellular and Molecular Medicine}, volume = {24}, journal = {Journal of Cellular and Molecular Medicine}, number = {5}, doi = {10.1111/jcmm.14910}, url = {http://nbn-resolving.de/urn:nbn:de:bvb:20-opus-214122}, pages = {2942 -- 2955}, year = {2020}, abstract = {Chronic myeloid leukaemia (CML) is a clonal myeloproliferative stem cell disorder characterized by the constitutively active BCR-ABL tyrosine kinase. The LIM and SH3 domain protein 1 (LASP1) has recently been identified as a novel BCR-ABL substrate and is associated with proliferation, migration, tumorigenesis and chemoresistance in several cancers. Furthermore, LASP1 was shown to bind to the chemokine receptor 4 (CXCR4), thought to be involved in mechanisms of relapse. In order to identify potential LASP1-mediated pathways and related factors that may help to further eradicate minimal residual disease (MRD), the effect of LASP1 on processes involved in progression and maintenance of CML was investigated. The present data indicate that not only overexpression of CXCR4, but also knockout of LASP1 contributes to proliferation, reduced apoptosis and migration as well as increased adhesive potential of K562 CML cells. Furthermore, LASP1 depletion in K562 CML cells leads to decreased cytokine release and reduced NK cell-mediated cytotoxicity towards CML cells. Taken together, these results indicate that in CML, reduced levels of LASP1 alone and in combination with high CXCR4 expression may contribute to TKI resistance.}, language = {en} }